Method for treating a complement mediated disorder caused by an infectious agent in a patient

Abstract

The present disclosure relates to, inter alia, a method of treating a complement mediated disorder caused by an infectious agents in a patient, comprising administering an effective amount of a C5 inhibitor, such as eculizumab or an eculizumab variant, to the patient.

1 . A method of treating a complement mediated disorder caused by an infectious agent in a human patient comprising administering an effective amount of a polypeptide inhibitor of human complement C5 protein to the human patient. 
     
     
         2 . The method of  claim 1 , wherein the infectious agent is selected from the group consisting of virus, bacteria, protozoa, fungi, prion and worm. 
     
     
         3 . The method of  claim 1 , wherein the infectious agent is a virus that can cause hemorrhagic fever in the patient. 
     
     
         4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein the complement mediated disorder is sepsis. 
     
     
         6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein the infectious agent is a virus that can cause VHF or the complement mediated disorder is sepsis. 
     
     
         8 . The method of  claim 1 , wherein the polypeptide inhibitor is a monoclonal antibody. 
     
     
         9 . The method of  claim 1 , wherein the polypeptide inhibitor comprises a variable region of an antibody. 
     
     
         10 . The method of  claim 1 , wherein the polypeptide inhibitor is eculizumab or an eculizumab variant, or antigen-binding fragment of either. 
     
     
         11 - 13 . (canceled) 
     
     
         14 . The method of  claim 3 , wherein the virus is a filovirus and wherein the filovirus is an Ebola virus. 
     
     
         15 . The method of  claim 1 , further comprising administering a second therapeutic agent to the patient. 
     
     
         16 - 23 . (canceled) 
     
     
         24 . The method of  claim 1 , wherein the polypeptide inhibitor of complement C5 is a polypeptide comprising one or more of the amino acid sequence depicted in SEQ ID NOs:1-3, 5-8, or 24, 26-33, or an antigen binding fragment of any of the above. 
     
     
         25 . The method of  claim 1 , wherein the polypeptide inhibitor of complement C5 is a polypeptide comprising one or more of the amino acid sequence depicted in SEQ ID NOs:9-16. 
     
     
         26 . (canceled) 
     
     
         27 . A method of treating a complement mediated disorder caused by an infectious agent in a human patient, comprising administering an effective amount of an anti-C5 antibody, or antigen binding fragment thereof, to the patient, wherein the complement mediated disorder is Shiga toxin-producing  E. coli  hemolytic uremic syndrome (STEC-HUS), wherein the method comprises an administration cycle comprising an induction phase followed by a maintenance phase, wherein:
 the anti-C5 antibody, or antigen binding fragment thereof, is administered during the induction phase at a dose of 900 mg weekly for 4 weeks, starting at day 0, and is administered during the maintenance phase at a dose of 1200 mg in week 5 and then 1200 mg every two weeks; or   the anti-C5 antibody, or antigen binding fragment thereof, is administered during the induction phase at a dose of 600 mg weekly for 2 weeks, starting at day 0, and is administered during the maintenance phase at a dose of 900 mg in week 3, and then 900 mg every two weeks; or   the anti-C5 antibody, or antigen binding fragment thereof, is administered during the induction phase at a dose of 600 mg weekly for 2 weeks, starting at day 0, and is administered during the maintenance phase at a dose of 600 mg in week 3, and then 600 mg every two weeks; or   the anti-C5 antibody, or antigen binding fragment thereof, is administered during the induction phase at a dose of 600 mg weekly for 1 week, starting at day 0, and is administered during the maintenance phase at a dose of 600 mg every week; or   the anti-C5 antibody, or antigen binding fragment thereof, is administered during the induction phase at a dose of 300 mg weekly for 1 week, starting at day 0, and is administered during the maintenance phase at a dose of 300 mg at week 2 and then every 3 weeks.   
     
     
         28 . The method of  claim 27 , wherein the anti-C5 antibody, or antigen binding fragment thereof, comprises CDR1, CDR2, and CDR3 heavy chain sequences as set forth in SEQ ID NOs:33, 29, and 11, respectively, and CDR1, CDR2, and CDR3 light chain sequences as set forth in SEQ ID NOs:12, 13, and 14, respectively. 
     
     
         29 . (canceled) 
     
     
         30 . The method of  claim 27 , wherein the anti-C5 antibody, or antigen binding fragment thereof, comprises a heavy chain variable region sequence as set forth in SEQ ID NO:15, and light chain variable region sequence as set forth in SEQ ID NO:16. 
     
     
         31 . The method of  claim 27 , wherein the anti-C5 antibody, or antigen-binding fragment thereof, comprises a heavy chain variable region depicted in SEQ ID NO:24 and a light chain variable region depicted in SEQ ID NO:16. 
     
     
         32 . (canceled) 
     
     
         33 . The method of  claim 27 , wherein the anti-C5 antibody, or antigen binding fragment thereof, comprises a heavy chain sequence as set for in SEQ ID NO:5, and light chain sequence as set forth in SEQ ID NO:6 or SEQ ID NO:8. 
     
     
         34 . The method of  claim 27 , wherein the antibody, or antigen-binding fragment thereof, comprises a heavy chain sequence depicted in SEQ ID NO:7 and a light chain sequence depicted in SEQ ID NO:6 or SEQ ID NO:8. 
     
     
         35 - 57 . (canceled) 
     
     
         58 . A kit for treating Shiga toxin-producing  E. coli  hemolytic uremic syndrome (STEC-HUS) in a human patient, the kit comprising:
 (a) a dose of an anti-C5 antibody, or antigen binding fragment thereof; and   (b) Instructions for using the anti-C5 antibody, or antigen binding fragment thereof, in the method of  claim 27 .   
     
     
         59 . An anti-C5 antibody, or antigen binding fragment thereof, comprising CDR1, CDR2 and CDR3 domains of the heavy chain variable region from the sequence set forth in SEQ ID NO:15 or SEQ ID NO:24, and CDR1, CDR2 and CDR3 domains of the light chain variable region from the sequence set forth in SEQ ID NO:16, for administration in a cycle comprising an induction phase followed by a maintenance phase, wherein:
 the anti-C5 antibody, or antigen binding fragment thereof, is administered during the induction phase at a dose of 900 mg weekly for 4 weeks, starting at day 0, and is administered during the maintenance phase at a dose of 1200 mg in week 5 and then 1200 mg every two weeks; or   the anti-C5 antibody, or antigen binding fragment thereof, is administered during the induction phase at a dose of 600 mg weekly for 2 weeks, starting at day 0, and is administered during the maintenance phase at a dose of 900 mg in week 3, and then 900 mg every two weeks; or   the anti-C5 antibody, or antigen binding fragment thereof, is administered during the induction phase at a dose of 600 mg weekly for 2 weeks, starting at day 0, and is administered during the maintenance phase at a dose of 600 mg in week 3, and then 600 mg every two weeks; or   the anti-C5 antibody, or antigen binding fragment thereof, is administered during the induction phase at a dose of 600 mg weekly for 1 week, starting at day 0, and is administered during the maintenance phase at a dose of 600 mg every week; or   the anti-C5 antibody, or antigen binding fragment thereof, is administered during the induction phase at a dose of 300 mg weekly for 1 week, starting at day 0, and is administered during the maintenance phase at a dose of 300 mg at week 2 and then every 3 weeks.